• Clinical science

Fifth disease (Erythema infectiosum)

Abstract

Erythema infectiosum (fifth disease) is one of the clinical syndromes caused by human parvovirus B19 infection. The virus is transmitted by respiratory droplets and primarily affects children between the ages of five and fifteen. Erythema infectiosum begins with a mild febrile illness followed two to five days later by a maculopapular rash that is especially noticeable on the cheeks (i.e., "slapped‑cheek" rash) and may be pruritic. Once the rash has appeared, the infected individual is no longer contagious and usually feels well again. Erythema infectiosum is self‑limiting, and the rash usually resolves within seven to ten days, but may be recurrent over several weeks. Whereas adult infection is characterized much more by arthritic symptoms and less by a rash, parvovirus B19 infection also manifests with joint symptoms in a minority of children. There is no specific vaccine or treatment for parvovirus B19 infection, though symptomatic treatment for arthralgias or pruritus can be used. Previous parvovirus B19 infection results in lifelong immunity against the virus. Because of its ability to infect erythrocyte progenitor cells, parvovirus B19 can cause transient anemia in infected patients, as well as complications such as a transient aplastic crisis in patients with chronic hemolytic diseases (e.g., sickle cell disease), and chronic pure red cell aplasia in the immunocompromised. Infection with parvovirus B19 (one of the TORCH congenital infections) during pregnancy may also have serious consequences for the fetus.

Epidemiology

  • Peak incidence: 5–15 years
  • Prevalence of seropositivity
    • ∼ 10% in preschool children
    • ∼ 70% in adults

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathogen

Route of transmission

  • Main route: aerosol
  • Other routes:
    • Hematogenous transmission
    • Transplacental transmission: In seronegative pregnant women, transmission to the unborn fetus may occur (in up to 30% of cases).

References:[4][5][6]

Pathophysiology

Parvovirus B19 binds to the P antigen (globoside) on erythroid progenitor cells → cellular invasion → viral DNA enters the nucleus of erythroid cells → viral DNA replication → cytotoxicity → clinical manifestations + transient cessation of erythropoiesis

Clinical features

Disease course

  • Incubation period: 4–14 days
  • Infectivity: Only contagious before onset of rash
  • Asymptomatic in ∼ 25% of cases

Clinical symptoms

  • Mild cold‑like symptoms
  • Exanthem: 2–5 days following the onset of cold‑like symptoms
    • Initial diffuse redness of the face with perioral sparing (slapped‑cheek rash)
    • Spread of exanthem to the extremities and trunk
      • Initially confluent and maculopapular; adopts a lace‑like, reticular appearance over time as it clears.
      • Associated with mild pruritus (in ∼ 50% of cases)
      • Fades after ∼ 7–10 days; may be recurrent over several weeks (becoming more pronounced after exposure to sunlight or heat)
    • Third phase with rash that varies with exposure to sun or heat and resolves spontaneously after several weeks.

Parvovirus B19-associated arthritis

  • Epidemiology: : affects < 10% of children and up to 60% of adults ( > ) infected with parvovirus B19
  • Clinical findings
    • Arthralgia with symmetrical, nondestructive polyarthritis, particularly in the joints of the fingers, hand, knee, and ankle
    • Usually resolves after 3–4 weeks
  • Complications: In some cases, persistent arthritis may develop (see “Complications” below).

References:[7][1][8][9][10][11]

Diagnostics

The diagnostic approach for parvovirus B19 infection varies by patient group. However, all groups may be affected by transient normocytic anemia with a low reticulocyte count because of the ability of the virus to infect erythrocyte progenitor cells.

Immunocompetent children

  • Erythema infectiosum is typically a clinical diagnosis (i.e., slapped‑cheek or lace‑like appearance of rash) in this patient population.

Immunocompetent adults

  • Lab tests only if diagnosis is unclear
  • Antibody testing
    • IgM antibody
      • Appears within ∼ 10 days of initial exposure, indicating acute illness
      • Remains positive for 2–3 months
    • IgG antibody
      • Appears approx. 2 weeks following infection
      • Remains positive for life
  • Differentiating between parvovirus B19‑associated arthritis and acute rheumatoid arthritis may require additional tests (see diagnostics section of rheumatoid arthritis)

Patients with transient aplastic crisis and immunocompromised patients

Pregnant women

References:[7][9][3]

Differential diagnoses

References:[7]

The differential diagnoses listed here are not exhaustive.

Treatment

References:[12][3]

Complications

References:[13][14][15]

We list the most important complications. The selection is not exhaustive.